The binding of spike S protein to the host cell receptor (angiotensin-converting enzyme 2-ACE2) mediates the entry of virus in the host lung tissue. During viral infection, TM protease serine 2 (TMPRSS2), a type 2 TM serine protease located on the host cell membrane, activates the S protein by cleaving it into S1 and S2 subunits, which activate the membrane fusion domain. After that, the viral RNA is copied, producing more viral particles in the host.

The total length of SARS-CoV-2 S protein is 1273 aa. It consists of a signal peptide (amino acids 1–13), the S1 subunit (14–685 residues), and the S2 subunit (686–1273 residues). The spike protein of SARS-CoV-2 is densely glycosylated as it contains 21 to 35 N-glycosylation sites. SARS-CoV-2 uses an extensively glycosylated spike (S) protein that protrudes from the viral surface to bind to angiotensin-converting enzyme 2 (ACE2) to mediate host-cell entry. Understanding the structure and function of SARS-CoV-2 S and the glycosylation of recombinant viral spikes can add value in getting additional information regarding the virus's invasion, pathogenesis, and fundamental features of viral biology, which will support the discovery of antiviral therapeutics and precision vaccine design.